RESUMEN

BACKGROUND: Fluoropyrimidines are chemotherapy drugs utilized to treat a variety of solid tumors. These drugs predominantly rely on the enzyme dihydropyrimidine dehydrogenase (DPD), which is encoded by the DPYD gene, for their metabolism. Genetic mutations affecting this gene can cause DPYD deficiency, disrupting pyrimidine metabolism and increasing the risk of toxicity in cancer patients treated with 5-fluorouracil. The severity and type of toxic reactions are influenced by genetic and demographic factors and, in certain instances, can result in patient mortality. Among the more than 50 identified variants of DPYD, only a subset has clinical significance, leading to the production of enzymes that are either non-functional or impaired. The study aims to examine treatment-related mortality in cancer patients undergoing fluoropyrimidine chemotherapy, comparing those with and without DPD deficiency. METHODS: The meta-analysis selected and evaluated 9685 studies from Pubmed, Cochrane, Embase and Web of Science databases. Only studies examining the main DPYD variants (DPYD*2A, DPYD p.D949V, DPYD*13 and DPYD HapB3) were included. Statistical Analysis was performed using R, version 4.2.3. Data were examined using the Mantel-Haenszel method and 95% CIs. Heterogeneity was assessed with I2 statistics. RESULTS: There were 36 prospective and retrospective studies included, accounting for 16,005 patients. Most studies assessed colorectal cancer, representing 86.49% of patients. Other gastrointestinal cancers were evaluated by 11 studies, breast cancer by nine studies and head and neck cancers by five studies. Four DPYD variants were identified as predictors of severe fluoropyrimidines toxicity in literature review: DPYD*2A (rs3918290), DPYD p.D949V (rs67376798), DPYD*13 (rs55886062) and DPYD Hap23 (rs56038477). All 36 studies assessed the DPYD*2A variant, while 20 assessed DPYD p.D949V, 7 assessed DPYD*13, and 9 assessed DPYDHap23. Among the 587 patients who tested positive for at least one DPYD variant, 13 died from fluoropyrimidine toxicity. Conversely, in the non-carrier group there were 14 treatment-related deaths. Carriers of DPYD variants was found to be significantly correlated with treatment-related mortality (OR = 34.86, 95% CI 13.96-87.05; p < 0.05). CONCLUSIONS: This study improves our comprehension of how the DPYD gene impacts cancer patients receiving fluoropyrimidine chemotherapy. Identifying mutations associated with dihydropyrimidine dehydrogenase deficiency may help predict the likelihood of serious side effects and fatalities. This knowledge can be applied to adjust medication doses before starting treatment, thus reducing the occurrence of these critical outcomes.

Asunto(s)

Dihidrouracilo Deshidrogenasa (NADP) , Fluorouracilo , Neoplasias , Humanos , Antimetabolitos Antineoplásicos/efectos adversos , Antimetabolitos Antineoplásicos/uso terapéutico , Deficiencia de Dihidropirimidina Deshidrogenasa/genética , Deficiencia de Dihidropirimidina Deshidrogenasa/metabolismo , Dihidrouracilo Deshidrogenasa (NADP)/genética , Dihidrouracilo Deshidrogenasa (NADP)/metabolismo , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/mortalidad , Farmacogenética

RESUMEN

INTRODUCTION:  The question of whether assisted reproductive technologies (ART) and ovulation induction are related to a higher incidence of ovarian tumors (OTs) is still controversial in the literature. METHODS: We performed a comprehensive search of PubMed, Embase, and Web of Science databases for case-control and cohort studies that investigated ART and ovulation induction exposure as risk factors for OT in infertile women. Odds ratios (OR) with 95% confidence intervals (CI) were employed for all endpoints. RESULTS: A total of nine case-control and twelve cohort studies were included, encompassing 439,477 women. ART was not associated with a higher risk of OTs (OR 1.05; 95% CI 0.86-1.29; p = 0.64; I2 = 36%), nor when considering only borderline OTs (OR 1.13; 95% CI 0.84-1.51; p = 0.42; I2 = 31%). In a subgroup analysis by study type, the risk difference of OTs remained non-significant for case-control (OR 1.12; 95% CI 0.70-1.78; p = 0.65; I2 = 60%) and cohort studies (OR 1.05; 95% CI 0.87-1.27; p = 0.60; I2 = 1%). For borderline OTs, the difference between groups was also non-significant for case-control studies (OR 1.44; 95% CI 0.73-2.87; p = 0.30; I2 = 40%) and cohort studies (OR 1.00; 95% CI 0.75-1.34; p = 0.99; I2 = 24%). CONCLUSION: In this systematic review and meta-analysis, ART exposure in infertile women was not associated with a higher risk of OTs in general or borderline tumors, even when accounting for study type differences.

RESUMEN

INTRODUCTION: Renal denervation has been associated with substantial and sustained blood pressure reduction and is considered to serve as an alternative treatment for patients with resistant hypertension. However, the first published SHAM-controlled trial assessing RDN safety and efficacy showed no difference between groups. AIM: We aimed to perform a meta-analysis quantifying the magnitude of blood pressure decrease secondary to renal denervation in patients with resistant hypertension. METHODS: Databases were searched for RCTs that compared RDN therapy to SHAM procedure and reported the outcomes of (1) 24-hour ambulatory blood pressure; (2) Office systolic blood pressure; (3) Daytime systolic blood pressure; and (4) Night-time systolic blood pressure. Mean differences with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was examined with I² statistics. P values of < 0.05 were considered statistically significant. Statistical analyses were performed using RStudio 4.2.3. RESULTS: Nine studies and 1622 patients were included. The AMBP [MD -3.72 95%CI -5.44, -2.00 p < 0.001; I²=34%] and DSBP [MD -4.10 95%CI -5.84, -2.37 p < 0.001; I²=0%] were significantly reduced in the RDN arm. ODBP [MD -6.04 95%CI -11.31, -0.78 p = 0.024; I²=90%] and NSBP [MD -1.81 95%CI -3.90, 0.27 p = 0.08; I²=0%] did not reach a statistically significant difference between groups. CONCLUSION: Renal denervation demonstrates greater efficacy in reducing 24-hour ambulatory and daytime systolic blood pressure in patients diagnosed with resistant hypertension.

Asunto(s)

Placebos , Terapéutica , Hipertensión , Presión Sanguínea , Desnervación

RESUMEN

INTRODUCTION: Renal denervation has been associated with substantial and sustained blood pressure reduction and is considered to serve as an alternative treatment for patients with resistant hypertension. However, the first published SHAM-controlled trial assessing RDN safety and efficacy showed no difference between groups. AIM: We aimed to perform a meta-analysis quantifying the magnitude of blood pressure decrease secondary to renal denervation in patients with resistant hypertension. METHODS: Databases were searched for RCTs that compared RDN therapy to SHAM procedure and reported the outcomes of (1) 24-hour ambulatory blood pressure; (2) Office systolic blood pressure; (3) Daytime systolic blood pressure; and (4) Night-time systolic blood pressure. Mean differences with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was examined with I² statistics. P values of < 0.05 were considered statistically significant. Statistical analyses were performed using RStudio 4.2.3. RESULTS: Nine studies and 1622 patients were included. The AMBP [MD -3.72 95%CI -5.44, -2.00 p < 0.001; I²=34%] and DSBP [MD -4.10 95%CI -5.84, -2.37 p < 0.001; I²=0%] were significantly reduced in the RDN arm. ODBP [MD -6.04 95%CI -11.31, -0.78 p = 0.024; I²=90%] and NSBP [MD -1.81 95%CI -3.90, 0.27 p = 0.08; I²=0%] did not reach a statistically significant difference between groups. CONCLUSION: Renal denervation demonstrates greater efficacy in reducing 24-hour ambulatory and daytime systolic blood pressure in patients diagnosed with resistant hypertension.

RESUMEN

PURPOSE: Metformin was the first medication targeting insulin resistance in PCOS, and it has been extensively studied as a metabolic treatment option. In recent years, inositols have emerged as potential treatment options for PCOS, but confidence in the available evidence supporting their use is limited. METHODS: We comprehensively searched PubMed, Embase, and Cochrane databases for RCTs comparing the use of combined metformin and inositol versus metformin alone in women with PCOS. A random-effects model was used to calculate the risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). A p-value of <0.05 was deemed as statistically significant. RESULTS: Six RCTs and 388 patients were included in the analysis, with follow-up ranging from 3 to 6 months. Combination therapy was significantly associated with improved menstrual cycle regularity (RR 1.56; 95% CI 1.01 to 2.41; p = 0.04), and lower values of modified Ferriman-Gallwey score (MD -0.97; 95% CI -1.53 to -0.40; p < 0.01) and LH/FSH ratios (MD -0.13; 95% CI -0.24 to -0.03; p = 0.01). Differences in acne (p = 0.58), body mass index (p = 0.13), fasting blood glucose (p = 0.07) and HOMA-IR (p = 0.25) were not statistically significant. CONCLUSION: In this meta-analysis of RCTs, combination therapy was associated with cycle regularization and reduction in hirsutism and LH/FSH ratio compared to metformin monotherapy. Further studies are needed to clarify the true benefits of the use of inositol in PCOS treatment.

RESUMEN

BACKGROUND: Renal denervation (RDN) is an innovative procedure designed to regulate the renal sympathetic nervous system for the control of arterial hypertension (HTN). RDN has emerged as an alternative for patients with resistant HTN. However, the clinical efficacy of RDN remains incompletely elucidated. METHODS: PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) comparing the use of RDN with sham procedure or pharmacological treatment in patients with resistant HTN. Statistical analyses were performed using R Studio 4.3.2 (R Foundation for Statistical Computing, Vienna, Austria). Heterogeneity was examined with the Cochran Q test I2 statistics. Mean difference (MD) with 95% confidence interval (CI) were pooled across trials. P values of <0.05 were considered statistically significant. The primary outcomes of interest were changes from baseline in systolic blood pressure (SBP), diastolic blood pressure (DBP), and serum creatinine. RESULTS: Twenty-one RCTs comprising 3345 patients were included in this meta-analysis, whereby 2004 (59.91%) received renal denervation and 1341 (40.09%) received pharmacological treatment or sham procedure. Follow-up ranged from 2 to 48 months. Compared to control group, RDN significantly reduced SBP (MD -3.53 mm Hg; 95% CI -5.94 to -1.12; p = 0.004; I2 = 74%) and DBP (MD -1.48 mm Hg; 95% CI -2.56 to -0.40; p = 0.007; I2 = 51%). Regarding serum creatinine (MD -2.51; 95% CI -7.90 to 2.87; p = 0.36; I2 = 40%), there was no significant difference between RDN and control groups. CONCLUSION: In this meta-analysis of RCTs of patients with resistant HTN, RDN was associated with a reduction in SBP and DBP compared to sham procedure or pharmacological treatment.

RESUMEN

INTRODUÇÃO O hiperparatireoidismo é considerado uma causa endócrina de hipertensão arterial (HA) secundária. Contudo, a natureza dessa associação é ainda controversa na literatura. RELATO DE CASO Paciente de sexo masculino, 53 anos de idade, com antecedente de HA desde os 30 anos, em estágio III ao diagnóstico, evoluiu com HA refratária apesar do uso de 7 classes de anti-hipertensivos: Olmesartana (40mg/dia), Anlodipino (10mg/dia), Clortalidona (25mg/dia), Espironolactona (25mg/dia), Atenolol (50mg/dia) e Hidralazina (150mg/dia), mantendo PA total de 135/95 na MAPA de 24h e apresentando retinopatia hipertensiva grau II e microalbuminúria. Ao longo do acompanhamento foi identificado hiperparatireoidismo normocalcêmico: paratormônio (PTH)= 117 pg/mL (VR: 18-88); cálcio sérico total= 8,9 mg/dL; 25-OH- vitamina D= 17,8 ng/mL, com evidência de captação tênue de formação nodular filiforme adjacente ao polo superior do lobo tireoidiano esquerdo (1,4cmx0,2cm) em cintilografia de paratireoide. Dada a ausência de sintomas e por se tratar de alteração discreta, optou-se por tratamento conservador com reposição de colecalciferol e carbonato de cálcio. No entanto, apesar da reposição ao longo de um ano, o PTH permaneceu elevado (118 pg/mL) e a HA continuou refratária. DISCUSSÃO Numerosos estudos observacionais reportam uma correlação positiva entre PTH e níveis de PA, tanto no hiperparatireoidismo primario como no secundário, independente da presença de hipercalcemia. Alem disso, evidência experimental aponta efeitos vasoativos diretamente atribuíveis ao PTH, assim como aumento da secreção de renina, promoção de rigidez arterial e hipertrofia ventricular. Apesar disso, uma relação causal ainda não foi definitivamente estabelecida e alguns autores sugerem inclusive causalidade reversa. No caso aqui exposto a hipótese de associação causal é sugerida pela refratariedade do quadro hipertensivo que acompanha a elevação sustentada dos níveis de PTH. A comprovação dessa causalidade se daria pelo controle da HA mediante a paratireoidectomia. No entanto, em casos limítrofes como o presente, o procedimento não é rotineiramente indicado, não sendo portanto possível assinar um veredito de cumplicidade.

Asunto(s)

Humanos , Masculino , Persona de Mediana Edad , Hipertensión

RESUMEN

Breast Cancer (BC) is one of the most common cancers diagnosed in population femmale and it has several subtypes, one of them being theexpressing human epidermal growth factor receptor 2 positive (HER2 +), one of the treatments for HER2+ breast cancer consists of chemotherapy plus trastuzumab deruxtecan. Several clinical trials have shown the effectiveness and safety of trastuzumabe deruxtecano in cancer patients, however, several Adverse Events (AEs) have been described and the decrease in left ventricular ejection has been singled out for more prominent analysis. Objective: We conducted a systematic review and meta-analysis to investigate the cardiovascular effects of Trastuzumab Deruxtecano and whether it can influence the appearance of reduced left ventricular ejection fraction.. METHODS: We performed a systematic search in Embase, PubMed and Cochrane databases for randomized controlled trials (RCTs) showed a decrease in left ventricular ejection fraction in patients using trastuzumab deruxtecan against Her-2-positive breast cancer compared to patients to used another's treatments against this disease. Mean difference (MD) with 95% confidence intervals (CI) were calculated using a random effects model. The heterogeneity was examined in the I2 statistic. P-values > 0.05 were considered statistically significant. The statistical analysis was carried out using R software version 4.2.3. RESULTS: A total of 3 RCTs were included, with a total of 1656 patients evaluated, 928 patients randomized to the use of Trastuzumab Deruxtecan and 728 patients to the use of other treatments according to medical choice, follow-up ranged from 10 to 38 months. There was a visible in the decrease in left ventricular ejection fraction, with a higher incidence in the group that used trastuzumab compared to the placebo group (RR: 5.73%; 95% CI 1.51 - 21.78; I2 33% ; P= 0.010466). Another important point is the discontinuation of treatment due to grade 2 adverse events, classified as reduced LVEF, where a higher incidence is seen in the group that used Trastuzumab Deruxtecan compared to the placebo group (RR 2.11%; 95% CI 1.54 - 2.89; P = 0.000003),7. CONCLUSION: In this meta-analysis, Trastuzumab Deruxtecan showed a relationship with a decrease in left ventricular ejection fraction, displaying the need for more studies to evaluate the cardiotoxicity of trastuzumab and its effects as a whole on the cardiovascular system.

Asunto(s)

Terapéutica , Neoplasias de la Mama , Enfermedades Cardiovasculares , Quimioterapia , Cardiotoxicidad , Trastuzumab , Interpretación Estadística de Datos , Receptores ErbB

RESUMEN

BACKGROUND: Contemporary understanding characterizes cardiotoxicity as a reduction in left ventricular ejection fraction (LVEF) by at least 10%, resulting in a final value below 53% in successive assessments. Nevertheless, breast cancer therapy can impact the cardiovascular system through various avenues. Cardiotoxicity is a known side effect of anthracycline chemotherapy, and the effectiveness of concomitant statin use in mitigating this risk is still unclear. PURPOSE: We aimed to evaluate the potential cardioprotective effects of statin exposure during anthracycline treatment. Our hypothesis posited that patients receiving statins during their treatment would experience a lesser decline in left ventricular ejection fraction (LVEF), lower levels of cholesterol and a reduced occurrence of cardiotoxicity compared to those not exposed to statins. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing statin versus placebo in patients undergoing anthracycline therapy. We searched PubMed, Embase and Cochrane for eligible trials. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was examined with I2 statistics. P values of < 0.05 were considered statistically significant. Statistical analysis were performed using R software version 4.2.3. RESULTS: A total of 4 RCTs comprising 580 patients were included, of whom 281 were randomized to statins and 299 to placebo. The follow up period ranged from 2.5 to 24 months, with participant ages varying between 36 to 68.9 in the intervention group and 37.9 to 72 in the control group. Compared with placebo, statins were significantly associated with a higher left ventricular ejection fraction (MD 2.57%; 95% CI 1.05-4.08; p<0.001; I2=0%), reduction in left ventricular systolic end-volume (MD -4.5 mL; 95% CI -7.57 to -1.44; p<0.004; I2=0%) and diastolic end-volume (MD -6.08 mL; 95% CI -11.27 to -0.9; p<0.021; I2=0%), with a low heterogeneity value. Statins also showed important reduction of total cholesterol (MD -46.28 mg/dL; 95% CI -71.3 to -21.25; p<0.001; I2=89%) and LDL-C (MD -39.45 mg/dL; 95% CI -52.27 to -26.64; p<0.001; I2=84%). CONCLUSIONS: In this metaanalysis of RCTs, the use of statins showed a correlation with improved cardiovascular parameters, indicating their effectiveness in minimizing cardiotoxicity in breast cancer patients undergoing anthracycline chemotherapy

Asunto(s)

Neoplasias de la Mama , Enfermedades Cardiovasculares , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Interpretación Estadística de Datos , Quimioterapia , Cardiotoxicidad

RESUMEN

INTRODUÇÃO: O Ultrassom Doppler de artérias renais (USD-AR) com análise de velocidade de pico sistólico (VPS) é utilizado na investigação inicial de pacientes com suspeita de hipertensão (HAS) renovascular com sensibilidade de 85% e especificidade de 92%. Se trata, no entanto, de avaliação sujeita a variabilidade examinador-dependente. Apresentamos o caso de uma paciente com HAS refratária com exames ultrassonográficos iniciais discordantes. RELATO DE CASO: Paciente de 60 anos, com diagnóstico de HAS desde os 48 anos, foi encaminhada para centro de referência após episódio de AVC isquêmico por suspeita de HAS secundária. MAPA de 24h na admissão mostrava PA média total de 204/122 mmHg em vigência de Losartana e Hidroclorotiazida. Após ajustes terapêuticos sequenciais, obteve-se redução parcial dos níveis tensionais (PA média total no MAPA de 24h: 164x95 mmHg, em vigência de 7 classes: Olmesartana, Clortalidona, Lercanidipino, Carvedilol, Espironolactona, Hidralazina e Alfametildopa), mantendose, no entanto, fora da meta de PA e configurando quadro de HAS refratária. Dois USD-AR foram realizados em serviços diferentes, revelando resultados contraditórios. O USD-AR1 mostrava rim direito excluído e VPS da AR esquerda de 235 cm/s, enquanto no USD-AR2 a VPS da AR esquerda foi de 22 cm/s e a origem da AR direita não foi visualizada por interposição gasosa. A paciente foi submetida a arteriografia renal que revelou obstrução proximal (70%) da AR esquerda e oclusão total da AR direita. Optouse por angioplastia com implante de stent em AR esquerda com bom resultado angiográfico (Fig.1) e evolução clínico-laboratorial favorável (MAPA: PA total média = 135x75 mmHg na vigência de 6 classes; Creatinina plasmática pré- e pós-angioplastia: 2,2 mg/dL e 1,4 mg/dL, respectivamente). DISCUSSÃO: O exame de USD-AR é útil no rastreio da HAS renovascular, mas sua acurácia é examinador-dependente. Por isso, frente a resultado negativo e alto grau de suspeita clínica a investigação deveria prosseguir com exames como a angiotomografia, a angiorressonância e a arteriografia, que é o padrão-ouro para a identificação de estenose de AR.

Asunto(s)

Humanos , Femenino , Persona de Mediana Edad , Ultrasonografía Doppler , Hipertensión , Hipertensión Renovascular , Angioplastia , Constricción Patológica , Indicadores de Calidad de la Atención de Salud , Accidente Cerebrovascular Isquémico

RESUMEN

BACKGROUND: Fluoropyrimidines are chemotherapy drugs utilized to treat a variety of solid tumors. These drugs predominantly rely on the enzyme dihydropyrimidine dehydrogenase (DPD), which is encoded by the DPYD gene, for their metabolism. Genetic mutations affecting this gene can cause DPYD deficiency, disrupting pyrimidine metabolism and increasing the risk of toxicity in cancer patients treated with 5-fluorouracil. The severity and type of toxic reactions are influenced by genetic and demographic factors and, in certain instances, can result in patient mortality. Among the more than 50 identified variants of DPYD, only a subset has clinical significance, leading to the production of enzymes that are either non-functional or impaired. The study aims to examine treatment-related mortality in cancer patients undergoing fluoropyrimidine chemotherapy, comparing those with and without DPD deficiency. METHODS: The meta-analysis selected and evaluated 9685 studies from Pubmed, Cochrane, Embase and Web of Science databases. Only studies examining the main DPYD variants (DPYD*2A, DPYD p.D949V, DPYD*13 and DPYD HapB3) were included. Statistical Analysis was performed using R, version 4.2.3. Data were examined using the Mantel-Haenszel method and 95% CIs. Heterogeneity was assessed with I2 statistics. RESULTS: There were 36 prospective and retrospective studies included, accounting for 16,005 patients. Most studies assessed colorectal cancer, representing 86.49% of patients. Other gastrointestinal cancers were evaluated by 11 studies, breast cancer by nine studies and head and neck cancers by five studies. Four DPYD variants were identified as predictors of severe fluoropyrimidines toxicity in literature review: DPYD*2A (rs3918290), DPYD p.D949V (rs67376798), DPYD*13 (rs55886062) and DPYD Hap23 (rs56038477). All 36 studies assessed the DPYD*2A variant, while 20 assessed DPYD p.D949V, 7 assessed DPYD*13, and 9 assessed DPYDHap23. Among the 587 patients who tested positive for at least one DPYD variant, 13 died from fluoropyrimidine toxicity. Conversely, in the non-carrier group there were 14 treatment-related deaths. Carriers of DPYD variants was found to be significantly correlated with treatment-related mortality (OR = 34.86, 95% CI 13.96-87.05; p < 0.05). CONCLUSIONS: This study improves our comprehension of how the DPYD gene impacts cancer patients receiving fluoropyrimidine chemotherapy. Identifying mutations associated with dihydropyrimidine dehydrogenase deficiency may help predict the likelihood of serious side effects and fatalities. This knowledge can be applied to adjust medication doses before starting treatment, thus reducing the occurrence of these critical outcomes.

Asunto(s)

Humanos , Farmacogenética , Neoplasias/tratamiento farmacológico , Deficiencia de Dihidropirimidina Deshidrogenasa/metabolismo , Fluorouracilo/efectos adversos , Antimetabolitos , Antineoplásicos/efectos adversos

RESUMEN

BACKGROUND Atherosclerotic cardiovascular disease (ASCVD), affects approximately 18.6 million individuals worldwide and poses a significant healthcare related challenge. Despite the established efficacy of both high-intensity statin monotherapy (HIS) and moderate-intensity statin plus ezetimibe (MIS+EZT) in ASCVD management, the optimal treatment strategy remains unclear. METHODS A thorough literature study was conducted across PubMed, Embase, and the Cochrane databases, focusing on studies that compared the effects of moderate-intensity statins plus ezetimibe with high-intensity statin monotherapy in ASCVD patients. RESULTS In the 13 included studies, involving 8,592 patients, 4,525 (52.67%) of which received moderate-intensity statin plus ezetimibe treatment. The follow-up period ranged from 4 to 156 weeks, with participant ages varying LDL-C from 55.2 to 71 years old. Analysis revealed significant MIS+EZT-associated with greater percentages of patients achieved the goal in Low-Density Lipoprotein (LDL-C) < 70 (Odds Ratio (OR) 1.76; 95% CI [1.26; 2.45]; p=0.001; I²=73%), LDL-C reduction (Mean Difference (MD) -5.05 mg/dL; 95% CI [-9.02;-1.07]; p<0.013; I²=56%;); Total Cholesterol reduction (MD -7.91 mg/ dL; 95% CI [-14.90; -0.91]; p<0.027; I²=60%); Triglycerides reduction (MD -8.20 mg/ dL; 95% CI [-13.05; -3.35]; p<0.001; I²=2%;); There was no statistical difference between groups in Drug Adverse reaction (Risk Ratio (RR) 1.19; 95% CI [0.79; 1.78]; p=0.404; I²=0%); and Drug intolerance (RR 0.78; 95% CI [0.32; 1.92]; p=0.584; I²=35%). CONCLUSIONS This meta-analysis highlights the effectiveness of MIS+EZT in improving significant lipid profile components for ASCVD patients, as can been seen through the greater percentage of patients achieving the LDL-C <70 mg/dL target and lower LDL-C, total cholesterol and triglycerides levels. Importantly, there were no significant differences in the occurrence of overall adverse events and adverse drug reactions between the two groups.

Asunto(s)

Combinación Ezetimiba y Simvastatina , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Ezetimiba

RESUMEN

INTRODUCTION: The efficacy of liraglutide for treating type 2 diabetes mellitus and obesity is well established, but their role in the treatment of weight regain after bariatric surgery remains unclear. METHODS: We searched PubMed, Embase, and Cochrane Library databases in January 2024. A random-effects model was employed to compute mean differences (MD) and events per 100 observations with 95% confidence intervals (CI) for continuous and binary endpoints. Statistical analysis was performed using R software. RESULTS: A total of 16 studies were included and 881 individuals. Patients were mostly female (50%), aged 36 to 55 years, with a mean body mass index (BMI) of 39.4 kg/m2, and had BS surgery 5 years prior. Over a mean follow-up time ranging from 3 months to 4 years, it was observed a statistically significant reduction in BMI (MD - 8.56 kg/m2; 95% CI 3.34 to 13.79; p < 0.01) and a mean reduction in total weight (MD - 16.03 kg; 95% CI 0.03 to 32.02; p = 0.05) after liraglutide use. Additionally, 65% of patients undertaking liraglutide showed total body weight loss (BWL) above 5% (65.8 events per 100 observations; 95% CI 54.96 to 75.20; p < 0.01), while 26% lost more than 10% of total BWL (26.77 events per 100 observations; 95% CI 19.17 to 36.02; p < 0.01). A limitation is a variability between the studies. CONCLUSIONS: Our findings support the use of liraglutide for weight management in patients who experience weight regain after BS. Liraglutide is well tolerated and promotes significant weight loss, providing clinicians with a therapeutic option for this clinical challenge.

Asunto(s)

Cirugía Bariátrica , Liraglutida , Obesidad Mórbida , Aumento de Peso , Pérdida de Peso , Humanos , Liraglutida/uso terapéutico , Aumento de Peso/efectos de los fármacos , Pérdida de Peso/efectos de los fármacos , Femenino , Obesidad Mórbida/cirugía , Obesidad Mórbida/tratamiento farmacológico , Adulto , Índice de Masa Corporal , Persona de Mediana Edad , Masculino , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Resultado del Tratamiento

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Background/Objectives: Although oxytocin administration is recommended for delayed labor progress, there is no consensus over the preferred optimal dose of oxytocin. We aimed to perform a meta-analysis of pregnancy outcomes comparing high-dose versus low-dose oxytocin regimens for augmentation of delayed labor. Methods: PubMed, Embase, and Cochrane databases were systematically searched for studies comparing high-dose with low-dose oxytocin for labor augmentation from inception up to May 2023. The outcomes assessed were cesarean rate, instrumental delivery rate, postpartum hemorrhage, neonatal death, and uterine tachysystole. Subgroup analysis was performed with randomized controlled trials (RCTs) and propensity-matched studies. Statistical analysis was performed using Rstudio. Heterogeneity was assessed with I2 statistics, and a random-risk effect was used if I2 > 50%. Results: Twenty-one studies met inclusion criteria, and eighteen were RCTs. A total of 14.834 patients were included, of whom 7.921 (53.3%) received high-dose and 6.913 (46.6%) received low-dose oxytocin during labor augmentation. No statistical differences were found in cesarean delivery, neonatal mortality, postpartum hemorrhage and vaginal instrumentation rate. However, uterine tachysystole incidence was significantly higher with high-dose oxytocin (95% Cl, 1.30-1.94, p = 0.3; 0.6; I2 = 9%). Conclusions: Labor augmentation with a low-dose oxytocin regimen is effective as with a high-dose regimen, but with significantly less uterine tachysystole events, which can lead to intrauterine and neonatal complications. Our findings suggest that a low-dose regimen may be safe and effective for labor augmentation in medical practice.

RESUMEN

BACKGROUND/OBJECTIVES: Although oxytocin administration is recommended for delayed labor progress, there is no consensus over the preferred optimal dose of oxytocin. We aimed to perform a meta-analysis of pregnancy outcomes comparing high-dose versus low-dose oxytocin regimens for augmentation of delayed labor. METHODS: PubMed, Embase, and Cochrane databases were systematically searched for studies comparing high-dose with low-dose oxytocin for labor augmentation from inception up to May 2023. The outcomes assessed were cesarean rate, instrumental delivery rate, postpartum hemorrhage, neonatal death, and uterine tachysystole. Subgroup analysis was performed with randomized controlled trials (RCTs) and propensity-matched studies. Statistical analysis was performed using Rstudio. Heterogeneity was assessed with I2 statistics, and a random-risk effect was used if I2 > 50%. RESULTS: Twenty-one studies met inclusion criteria, and eighteen were RCTs. A total of 14.834 patients were included, of whom 7.921 (53.3%) received high-dose and 6.913 (46.6%) received low-dose oxytocin during labor augmentation. No statistical differences were found in cesarean delivery, neonatal mortality, postpartum hemorrhage and vaginal instrumentation rate. However, uterine tachysystole incidence was significantly higher with high-dose oxytocin (95% Cl, 1.30-1.94, p = 0.3; 0.6; I2 = 9%). CONCLUSIONS: Labor augmentation with a low-dose oxytocin regimen is effective as with a high-dose regimen, but with significantly less uterine tachysystole events, which can lead to intrauterine and neonatal complications. Our findings suggest that a low-dose regimen may be safe and effective for labor augmentation in medical practice.

Asunto(s)

Embarazo , Oxitocina/administración & dosificación , Interpretación Estadística de Datos

RESUMEN

INTRODUCTION: The efficacy of liraglutide for treating type 2 diabetes mellitus and obesity is well established, but their role in the treatment of weight regain after bariatric surgery remains unclear. METHODS: We searched PubMed, Embase, and Cochrane Library databases in January 2024. A random-effects model was employed to compute mean differences (MD) and events per 100 observations with 95% confidence intervals (CI) for continuous and binary endpoints. Statistical analysis was performed using R software. RESULTS: A total of 16 studies were included and 881 individuals. Patients were mostly female (50%), aged 36 to 55 years, with a mean body mass index (BMI) of 39.4 kg/m2, and had BS surgery 5 years prior. Over a mean follow-up time ranging from 3 months to 4 years, it was observed a statistically significant reduction in BMI (MD - 8.56 kg/m2; 95% CI 3.34 to 13.79; p < 0.01) and a mean reduction in total weight (MD - 16.03 kg; 95% CI 0.03 to 32.02; p = 0.05) after liraglutide use. Additionally, 65% of patients undertaking liraglutide showed total body weight loss (BWL) above 5% (65.8 events per 100 observations; 95% CI 54.96 to 75.20; p < 0.01), while 26% lost more than 10% of total BWL (26.77 events per 100 observations; 95% CI 19.17 to 36.02; p < 0.01). A limitation is a variability between the studies. CONCLUSIONS: Our findings support the use of liraglutide for weight management in patients who experience weight regain after BS. Liraglutide is well tolerated and promotes significant weight loss, providing clinicians with a therapeutic option for this clinical challenge.

Asunto(s)

Pérdida de Peso , Índice de Masa Corporal , Cirugía Bariátrica , Liraglutida/administración & dosificación , Interpretación Estadística de Datos

RESUMEN

BACKGROUND: Locally advanced rectal cancer (LARC) typically involves neoadjuvant chemoradiotherapy (nCRT) followed by surgery (total mesorectal excision, TME). While achieving a complete pathological response (pCR) is a strong indicator of a positive prognosis, the specific benefits of adjuvant chemotherapy after pCR remain unclear. To address this knowledge gap, we conducted a systematic review and meta-analysis to assess the potential advantages of adjuvant therapy in patients who achieve pCR. METHODS: In this study, we searched Medline, Embase, and Web of Science databases for relevant research. We focused on binary outcomes, analyzing them using odds ratios (ORs) with 95% confidence intervals (CIs). To account for potential variability between studies, all endpoints were analyzed with DerSimonian and Laird random-effects models. We assessed heterogeneity using the I2 statistic and employed the R statistical software (version 4.2.3) for all analyses. RESULTS: Thirty-four studies, comprising 31,558 patients, were included. The outcomes demonstrated a significant difference favoring the AC group in terms of overall survival (OS) (HR 0.75; 95% CI 0.60-0.94; p = 0.015; I2 = 0%), and OS in 5 years (OR 1.65; 95% CI 1.21-2.24; p = 0.001; I2 = 39%). There was no significant difference between the groups for disease-free survival (DFS) (HR 0.94; 95% CI 0.76-1.17; p = 0.61; I2 = 17%), DFS in 5 years (OR 1.19; 95% CI 0.82-1.74; p = 0.36; I2 = 43%), recurrence-free survival (RFS) (HR 1.10; 95% CI 0.87-1.40; p = 0.39; I2 = 0%), and relapse-free survival (OR 1.08; 95% CI 0.78-1.51; p = 0.62; I2 = 0%). CONCLUSION: This systematic review and meta-analysis found a significant difference in favor of the ACT group in terms of survival after pCR. Therefore, the administration of this treatment as adjuvant therapy should be encouraged in clinical practice.

Asunto(s)

Neoplasias del Recto , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Neoplasias del Recto/mortalidad , Neoplasias del Recto/tratamiento farmacológico , Quimioterapia Adyuvante , Resultado del Tratamiento , Análisis de Supervivencia , Supervivencia sin Enfermedad , Terapia Neoadyuvante

RESUMEN

BACKGROUND: Locally advanced rectal cancer (LARC) typically involves neoadjuvant chemoradiotherapy (nCRT) followed by surgery (total mesorectal excision, TME). While achieving a complete pathological response (pCR) is a strong indicator of a positive prognosis, the specific benefits of adjuvant chemotherapy after pCR remain unclear. To address this knowledge gap, we conducted a systematic review and meta-analysis to assess the potential advantages of adjuvant therapy in patients who achieve pCR. METHODS: In this study, we searched Medline, Embase, and Web of Science databases for relevant research. We focused on binary outcomes, analyzing them using odds ratios (ORs) with 95% confidence intervals (CIs). To account for potential variability between studies, all endpoints were analyzed with DerSimonian and Laird random-effects models. We assessed heterogeneity using the I2 statistic and employed the R statistical software (version 4.2.3) for all analyses. RESULTS: Thirty-four studies, comprising 31,558 patients, were included. The outcomes demonstrated a significant difference favoring the AC group in terms of overall survival (OS) (HR 0.75; 95% CI 0.60-0.94; p = 0.015; I2 = 0%), and OS in 5 years (OR 1.65; 95% CI 1.21-2.24; p = 0.001; I2 = 39%). There was no significant difference between the groups for disease-free survival (DFS) (HR 0.94; 95% CI 0.76-1.17; p = 0.61; I2 = 17%), DFS in 5 years (OR 1.19; 95% CI 0.82-1.74; p = 0.36; I2 = 43%), recurrence-free survival (RFS) (HR 1.10; 95% CI 0.87-1.40; p = 0.39; I2 = 0%), and relapse-free survival (OR 1.08; 95% CI 0.78-1.51; p = 0.62; I2 = 0%). CONCLUSION: This systematic review and meta-analysis found a significant difference in favor of the ACT group in terms of survival after pCR. Therefore, the administration of this treatment as adjuvant therapy should be encouraged in clinical practice.

Asunto(s)

Neoplasias del Recto/terapia , Análisis de Supervivencia , Resultado del Tratamiento , Quimioterapia Adyuvante , Terapia Neoadyuvante

RESUMEN

INTRODUCTION: New therapies for resistant hypertension (RH), including renal denervation (RDN), have been studied. AIM: Access the safety and effectiveness of radiofrequency-based RDN vs pharmacological treatment for RH. METHODS: A thorough literature search was conducted across PubMed, EMBASE, and the Cochrane databases, focusing on studies that compared the effects of radiofrequency-based RDN versus pharmacological treatment for RH. Treatment effects for binary and continuous endpoints were pooled and used, respectively, odds-ratio (OR) and mean differences (MD) with 95% confidence intervals (CI) to analyze continuous outcomes. RESULTS: In the 10 included studies, involving 1.182 patients, 682 received radiofrequency-based RDN. The follow-up period ranged from 6 to 84 months. Analysis revealed that the RDN group had a significant reduction in office systolic blood pressure (BP) (MD − 9.5 mmHg; 95% CI − 16.81 to − 2.29; P = 0.01), office diastolic BP (MD − 5.1 mmHg; 95% CI − 8.42 to − 2.80; P < 0.001), 24 h systolic BP (MD − 4.8 mmHg; 95% CI − 7.26 to − 2.42; P < 0.001). For 24 h diastolic BP RDN did not have a significant reduction (MD − 2.3 mmHg; 95% CI − 4.19 to − 0.52; P = 0.012). The heterogeneity between the studies was high, visible in the funnel and Baujat plots. The OR was non-significant for non-serious adverse events, but also clinically significant for hypertensive crises and strokes for the RDN group. CONCLUSIONS: While the pharmacological regimen of 3 or more anti-hypertensive, including a diuretic, still be the first-line option for RH treatment, our results support that radiofrequency-based RDN is superior in reducing global BP and is safe.

RESUMEN

INTRODUCTION: New therapies for resistant hypertension (RH), including renal denervation (RDN), have been studied. AIM: Access the safety and effectiveness of radiofrequency-based RDN vs pharmacological treatment for RH. METHODS: A thorough literature search was conducted across PubMed, EMBASE, and the Cochrane databases, focusing on studies that compared the effects of radiofrequency-based RDN versus pharmacological treatment for RH. Treatment effects for binary and continuous endpoints were pooled and used, respectively, odds-ratio (OR) and mean differences (MD) with 95% confidence intervals (CI) to analyze continuous outcomes. RESULTS: In the 10 included studies, involving 1.182 patients, 682 received radiofrequency-based RDN. The follow-up period ranged from 6 to 84 months. Analysis revealed that the RDN group had a significant reduction in office systolic blood pressure (BP) (MD - 9.5 mmHg; 95% CI - 16.81 to - 2.29; P = 0.01), office diastolic BP (MD - 5.1 mmHg; 95% CI - 8.42 to - 2.80; P < 0.001), 24 h systolic BP (MD - 4.8 mmHg; 95% CI - 7.26 to - 2.42; P < 0.001). For 24 h diastolic BP RDN did not have a significant reduction (MD - 2.3 mmHg; 95% CI - 4.19 to - 0.52; P = 0.012). The heterogeneity between the studies was high, visible in the funnel and Baujat plots. The OR was non-significant for non-serious adverse events, but also clinically significant for hypertensive crises and strokes for the RDN group. CONCLUSIONS: While the pharmacological regimen of 3 or more anti-hypertensive, including a diuretic, still be the first-line option for RH treatment, our results support that radiofrequency-based RDN is superior in reducing global BP and is safe.

Asunto(s)

Antihipertensivos , Presión Sanguínea , Ablación por Catéter , Resistencia a Medicamentos , Hipertensión , Riñón , Simpatectomía , Humanos , Resultado del Tratamiento , Hipertensión/fisiopatología , Hipertensión/cirugía , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Presión Sanguínea/efectos de los fármacos , Antihipertensivos/uso terapéutico , Antihipertensivos/efectos adversos , Ablación por Catéter/efectos adversos , Riñón/inervación , Persona de Mediana Edad , Simpatectomía/efectos adversos , Simpatectomía/métodos , Femenino , Masculino , Anciano , Factores de Riesgo , Arteria Renal/inervación , Arteria Renal/cirugía , Factores de Tiempo , Adulto